Fluid dispensing device

ABSTRACT

The invention concerns a fluid dispensing device, characterised in that it comprises: a dispensing member ( 10 ) including: a conduit ( 42, 44 ) allowing through a transporting liquid ( 52 ), a valve ( 48 ) fixed to one of the ends ( 38 ) of said conduit, a dispensing needle ( 12 ) arranged at the other end ( 38 ), means for measuring the flow rate ( 46 ) of the transporting liquid ( 52 ) in the conduit, control means ( 54 ) for circulating the said liquid through said conduit in one direction or the other, and electronic means ( 58, 60 ) reacting to said measuring means ( 46 ) and acting both on said valve ( 48 ) and said control means ( 54 ) to cause a specific amount of fluid ( 30 ) to be sucked into the needle ( 12 ), and then to be restored.

The present invention relates to fluid dispensing devices. It relatesmore especially to a device intended to deliver very small volumes,typically from 0.001 to a few μl, with great precision.

Such a device is described in U.S. Pat. No. 5,916,524. It comprises aneedle for dispensing a fluid into a target and which is connected to anassembly comprising:

-   -   a syringe forming a housing and equipped with a plunger actuated        by a stepping motor,    -   a tube connecting the syringe to the needle, and    -   a set of valves associated with the tube and, initially,        allowing the syringe to be filled from a container and then,        commanding the flow of the fluid through the tube towards the        needle, the amount dispensed being defined by the number of        steps effected by the stepping motor.

In most applications, the fluid to be dispensed needs to be very pure.It is therefore expensive and tricky to handle. In addition, thequantities needed may be extremely small. Now, with the device describedhereinabove, the liquid passes from the container into the syringe, thenfrom the latter into the needle, through the tube and the valves. Thevolume thus involved and the risk of contamination are great.Furthermore, it is difficult to control the amount dispensed. This isbecause the volume of fluid lying between the syringe and the end of theneedle is great and can vary appreciably, particularly throughdeformation of the tube when this tube is flexible.

Another device, which is similar, is described in U.S. Pat. No.5,927,547. It comprises:

-   -   a dispenser formed of a piezoelectric micro-dosing device,    -   a syringe fitted with a plunger and forming a housing,        controlled by a stepping motor,    -   a pressure sensor, and    -   first and second tubes respectively connecting the syringe to        the sensor and connecting the sensor to the micro-dosing device.

In this device, the syringe, the sensor and the first tube, togetherwith part of the second tube, contain a transporter liquid. A fluid fordispensing, in this case a liquid also, arranged in a source, is drawnup by the plunger into the micro-dosing device as far as the secondtube, with an air bubble interposed between the transporter liquid andthe fluid.

The fluid for dispensing is ejected from the micro-dosing device byapplying a signal to the piezoelectric part, which generates a shockwavecausing a droplet of known volume, dependent on the dimensions of themicro-dosing device and on the characteristics of the fluid concerned,to be emitted.

Control means check, via the sensor, that the pressure of the transportliquid remains constant, thus ensuring correct operation of themicro-dosing device. This pressure is adjusted by sending pulses to thestepping motor, which controls the plunger of the syringe. In order todispense fluid only into charged targets, the micro-dosing device has acapacitive level sensor at its free end.

The piezoelectric micro-dosing device allows very small volumes, whichmay be of the order of 5 picolitres, to be delivered. The maximumachievable flow rate is unfortunately limited, which means that the timetaken to dispense quantities of fluid of the order of a μl makes such adevice somewhat lacking. In addition, the volume available in themicro-dosing device is relatively modest, which means that if excessivenumbers of movements between the source and the target are to beavoided, the fluid for dispensing needs to be loaded not only into themicro-dosing device, but also into the tube connecting it to the sensor.There is therefore also a certain risk of contamination.

It should finally be pointed out that the use of a piezoelectric systemfor commanding the ejection of the fluid for dispensing gives the devicea discrete operation which necessarily limits its precision.

Document WO 98/45205 proposes an improved version of the deviceaccording to U.S. Pat. No. 5,927,547. In this case, the transporterliquid is displaced by placing its reservoir at a reduced pressure, sothat a determined quantity of fluid is drawn up into the piezoelectricmicro-dosing device under the control of a flow sensor.

Such a device does, however, still suffer from the use of apiezoelectric dosing device for ejecting the fluid that is to bedispensed.

The object of the present invention is to propose a dispensing devicethat does not use a piezo micro-dosing device or equivalent element.This object is achieved by virtue of the fact that it comprises:

-   -   a duct for the passage of a transporter liquid,    -   a valve fixed to one of its ends,    -   a dispensing needle arranged at its other end,    -   means of measuring the rate of flow of the transporter liquid in        the duct,    -   a sealed container containing the transporter liquid and        connected to the valve by a tube,    -   a pump of the intake and delivery type, in communication with        the container and serving to place the latter at a raised        pressure or at a reduced pressure so as to cause the liquid to        flow through the said duct in one direction or the other, and    -   electronic means responding to the said flow measurement means        and acting both on the said valve and on the said pump so as to        cause a determined amount of fluid to be drawn up into the        needle then delivered.

In such a dispensing device, the fluid is drawn up and ejected onlyunder the command of the measuring means of the rate of flow of thetransporter liquid, by placing the container of said liquid at a reducedpressure or at a raised pressure. Thus, it is no longer necessary, as itis the case with devices according to documents U.S. Pat. No. 5,927,547and WO 98/45205, to associate the needle with a piezoelectric system andthe high voltage electronic circuit which controls it.

The cost of the device is thus strongly reduced and its reliability isimproved. Moreover, the ejection of the fluid by a merely “passive”needle insures a continuous mode of operation whereas the ejection by apiezo is made in a discrete way. The precision is thus improved.Advantageously, the duct is formed inside an elongate body bearing, atits respective ends, the valve and the needle and, in its centralportion, the said flow measurement means which are inserted in the pathof the duct, in communication therewith. The dispensed volume is thusmeasured in the optimum way.

For certain applications, in which very small volumes are used,experience has shown that it is advantageous for the duct to be formedinside an elongate body bearing, at its respective ends, the valve andthe needle and for the flow measurement means to be inserted in the pathof the duct, upstream of the valve.

According to a preferred embodiment, the flow measurement means are ofthe type that provides a measurement of the pressure difference betweentwo points on the duct and a measurement of the temperature.

In this embodiment, the electronic means may be designed to analyseinformation from the flow measurement means and to provide informationon the conditions of dispensing of the fluid.

The electronic means advantageously comprise:

-   -   means of calculating the amount of fluid drawn into or delivered        through the needle, on the basis of the information supplied by        the flow measurement means, and    -   a control circuit placed under the command of the said        calculating means and mainly performing the functions of        controlling the pump to place the said container at a raised        pressure or at a reduced pressure and of commanding the opening        and closing of the valve so as to allow or disallow the        displacement of a determined amount of transport liquid in one        direction or the other.

As a preference, the calculating means hold, in memory, the values ofthe viscosity of the transport liquid as a function of temperature andare programmed to calculate, on the basis of the pressure andtemperature information delivered by the said flow measurement means,the amount of fluid drawn into or delivered through the needle.

Finally, it is particularly advantageous for the electronic means to bedesigned, in addition, to detect that a drop of fluid attached to theend of the needle is in contact with a target.

It is useful to note that the device as described hereinabove makes itpossible precisely to measure the volume of fluid both when it is drawnup and when it is dispensed. It is thus possible to prepare doses of oneor several fluids, separated by an air bubble, these doses then beingdispensed into the targets.

Other advantages and features of the invention will become apparent fromthe description which will follow, given with respect to the appendeddrawing, in which:

FIG. 1 is the operating diagram of a fluid dispensing device in itssurroundings, and

FIG. 2 shows, in greater detail, the structure of the device accordingto the invention.

FIG. 1 shows, schematically, an assembly comprising a fluid dispenser 10equipped with a dispensing needle 12 and a control cabinet 14. A tube 16and a cable 18 connect the dispenser 10 to the cabinet 14.

The assembly further comprises a robot 20 of the Cartesian type, formedof a horizontal table 22, of a portal frame 24 mounted so that it canmove in translation over the table in a direction perpendicular to theplane of the figure, and of a carriage 26 mounted so that it can move inhorizontal translation along the portal frame in a direction parallel tothe plane of the figure. The dispenser 10 is mounted so that it can movein vertical translation on the carriage 26, so that it can thus movealong three mutually orthogonal axes. A source 28 containing a fluid 30and a target 32 are arranged on the table 22, in the space swept by theportal frame 24.

The assembly depicted in FIG. 1 is intended to allow precise transfer ofthe fluid 30, by means of the dispenser 10, from the source 28 to thetarget 32.

Both the source 28 and the target 32 may be a test specimen, amicrotitration plate (of type 96, 384 or 1536 for example) or any othersurface or reservoir of liquid arranged in any spatial formatwhatsoever. The fluid 30 is generally a liquid, but could just as easilybe a gas. In this case, the source 28 is a sealed container closed by amembrane able to be perforated and the needle 12 is of a type similar tothose used for hypodermic injections, for example.

Reference will now be made to FIG. 2 which, in greater detail, shows thedispenser 10 and the control cabinet 14.

The dispenser 10 comprises a support 34 intended to be fitted to thecarriage 26 and bearing an elongate body 36, advantageously made ofchemically inert plastic, such as the material known by the name ofPEEK, of cylindrical overall shape and mounted vertically. At each endit has a cylindrical housing 38 and, in its central portion, it has acavity 40. It is also pierced, along its axis, with an upper duct 42opening, on the one hand, into the upper housing 38 and, on the otherhand, into the cavity 40 and with a lower duct 44 opening, on the onehand, into the lower housing 38 and, on the other hand, into the cavity40.

The cavity 40 houses a flow meter 46, made on a ceramic tablet and whichis positioned in such a way as to find itself in sealed communicationwith the ends of the ducts 42 and 44. It is advantageously fixed byclamping, with the insertion of seals.

The upper housing 38 houses, in a sealed and removable manner, via anappropriate adapter, a valve 48 the function of which is to place theupper duct 42 in communication with the tube 16.

At the other end of the body 36, the lower housing 38 houses, also in asealed and removable manner, via an appropriate adapter, the end of thedispensing needle 12.

The needle 12 is chosen according to the way in which the fluid 30 is tobe dispensed to the target 32 and according to the volume to bedispensed, as will be specified later on.

The material of which the needle 12 is made must not react with thefluid. Stainless steel may, for example, be used in many cases. Thebasic material may or may not be covered with a layer improving thewettability or non-wettability properties of certain internal orexternal surfaces of the needle.

The length and the bore of the needle 12 are chosen according to thequantity of fluid to be dispensed to the target 32 in one or more shots.These dimensions are defined in such a way that the volume of the boreof the needle is greater than the volume of fluid to be dispensed in asingle shot. It is thus possible for the volume in question to be drawnup in such a way that it is entirely housed in the needle, somethingwhich affords various advantages.

Specifically, once the fluid 30 can remain confined to the needle 12,when there is a wish to dispense another fluid, all that is required isfor this needle to be changed rather than for the whole dispenser tohave to be cleaned. It is thus possible, during one and the samesequence, to dispense several fluids, in highly varying quantities,without that posing any problem. To do this, all that is required is forthe needle to be changed, something that a robot can do with nodifficulty.

It is also possible to dispense highly corrosive fluids, simply bychoosing an appropriate needle.

In other words, these advantages stem from the fact that there is nointerference between the fluid or fluids for dispensing and thecomponents of the dispenser 10 other than the needle 12.

The flow meter 46 plays an important part in the correct operation ofthe device because it needs to be able, precisely, to measure a volumeof a few nanolitres. It is advantageous for this purpose to use the flowmeter described in the publication entitled “A Differential PressureLiquid Flow Sensor for Flow Regulation and Dosing Systems” by M. A.Boillat et al. 0-7803-2503-6© 1995 IEEE. This flow meter comprisessensors making it possible to measure a pressure difference between itsinlet and its outlet, and the temperature of the fluid passing throughit. Once these two parameters have been determined, it is possible tocalculate the flow rate, provided that the viscosity of the transportliquid as a function of its temperature is known.

As FIG. 2 shows, the control cabinet 14 comprises a sealed container 50partially filled with a transport liquid 52 into which the tube 16connected to the valve 48 dips. A pump 54, of the intake and deliverytype, is in communication, via a duct 56, with the upper part of thecontainer situated above the liquid 52.

The liquid 52 is chosen according to the fluid 30 for dispensing so thatthese liquids are, from the chemical point of view, neutral with respectto each other. It will be noted that the liquid 52 fills the tube 16 andpasses through the dispenser 10 as far as the needle 12, as will bespecified later on.

The pump 54 allows the container 50 to be placed at a raised pressure orat a reduced pressure. In that way, when the valve 48 is opened, theliquid 52 can be displaced from the container 50 to the needle 12 or inthe other direction.

A control circuit 58 is connected to the pump 54, to the valve 48 and tothe flow meter 46. It is under the command of a computer 60 to performthe following main functions:

-   -   controlling the pump 54 with a view to placing the container 50        at a raised pressure or at a reduced pressure,    -   commanding the opening and closing of the valve 48 allowing or        disallowing the displacement of the liquid 52 in one direction        or the other,    -   transmitting to the computer 60 the pressure and temperature        measurements from the flow meter 46.

The computer 60 serves to program and coordinate the assembly. It thuscontrols the movements of the robot 20 to cause the dispenser 10 to goand find doses of fluid 30 from the source 28 and deposit them on thetarget 32. In addition, it holds in its memory the values of theviscosity of the transport liquid as a function of temperature. Thatallows it, on the basis of the pressure and temperature informationdelivered by the flow meter 46, to determine, precisely and in realtime, the amount of fluid drawn up into or delivered through the needle12. It is thus possible to retain in memory the exact quantities offluid 30 dispensed each time. Furthermore, analysis of the signalsemitted by the flow meter 46 makes it possible to detect malfunctions inthe device, such as sealing problems or problems of blockages in theducts 42 or 44.

The device which has just been described allows a fluid 30 to betransferred between the source 28 and the target 32 in a particularlyeffective and economical way. This operation is performed as follows.

First of all, the transporter liquid 52 is introduced into the container50. The latter is then closed and the pump 54 is activated, so as toplace the container 46 at a raised pressure. The valve 48 is thenopened, so that the liquid 52 enters the tube 16 and passes through thedispenser 10 as far as the needle 12 which it completely fills. Thevalve 48 is then closed.

During this operation it is essential to make sure that no air bubblesremain trapped in the tube 16, as this would degrade the performance ofthe device. This check can be done automatically, by analysing thesignals emitted by the flow meter. Indeed it is found that the presenceof air bubbles leads to elasticity in the ducts 42 and 44, and thisslows the pressure rise when the valve is open.

The device 10 is now ready to take fluid 30 from the source 28 todeliver it to the target 32. For this, the container 50 is placed at areduced pressure by the pump 54 and the robot 20 brings the needle 12over the source 28.

According to an advantageous mode of operation, a small amount of air isfirst of all drawn up by the needle 12 so as to form a bubble betweenthe liquid 52 and the fluid 30 for dispensing. For this, the valve 48 isopened and the liquid 52 rises up in the needle 12 towards the container50, through the flow meter 46 whose output signal allows the controlcircuit 58 to calculate the volume of air drawn in, that is to say thevolume of the bubble. When the measured volume reaches the desired valuecontained in the computer 60, the valve 48 is closed and the robot 20introduces the needle 12 into the fluid 30.

When the latter is a liquid, which it generally is, the flow meter 46records a sudden variation in pressure when the needle 12 goes in. Thecomputer 60 can thus determine the position of the needle 12 withrespect to the surface of the fluid 30. It then gives the robot 20 theorder to plunge the needle 12 into the fluid 30 far enough to avoid theformation of parasitic bubbles during suction. The valve is then openedagain so that the drawing-up operation can begin.

When, on the basis of the information supplied by the flow meter 46, thecomputer 60 determines that the desired amount of fluid has been drawnup into the needle 12, the valve 48 is closed again.

It is possible to repeat this operation several times so that the needle12 can contain several doses of fluid 30, each separated by an airbubble.

As an alternative, the fluid 30 can be drawn up without theinterposition of an air bubble. The needle 12 is then plunged directlyinto the fluid 26 and the drawn-up volume is determined as describedabove, but in a single shot.

When the needle 12 is filled with the fluid for dispensing, the robot 20takes the dispenser 10 over the target 32 and the pump 54 places thecontainer 50 at a raised pressure. The valve 48 is then opened to allowthe fluid to be ejected and closed again when the measured volumecorresponds to the volume set by the computer.

The dimensions of the needle bore play an important part, especiallywhen the end of this needle is in the air. In this case, precisedispensing can be achieved only if the fluid 30 flows out uniformly.What this amounts to is that it is necessary to avoid drops formingduring the dispensing operation. A suitable choice of the pressure inthe container 50 and of the bore at the free end of the needle 12 allowssatisfactory operation to be ensured.

When a small volume needs to be dispensed, it is advantageous to use aneedle having a narrowing of the hole at its free end, this being wellknown by the term “nozzle”. It is also advantageous for the flow meter46 to be upstream of the valve 48. Indeed, experience has shown that theflow can be well controlled in this way, even with low flow rates.

It goes without saying that the device according to the invention can beused in yet other conditions. It is thus also possible to dispense agas. In this case, the needle is introduced into a sealed bottle, inplace of the source 24, which contains the gas and the liquid. A volumeof gas is drawn up, as explained above with regard to the air, followedby a drop of liquid, so that the gas is trapped in the needle bysuccessive bubbles of tailored volume. This gas is then dispensed into atarget by injecting into it a volume corresponding to the volume of thegas and of the drop separating two successive bubbles.

1. Fluid dispensing device characterized in that it comprises: adispensing member (10) comprising: a duct (42, 44) for the passage of atransporter liquid (52), a valve (48) fixed to one of the ends (38) ofthe said duct, a passive dispensing needle (12) arranged at the otherend (38), and means (46) of measuring the rate of flow of thetransporter liquid (52) in the duct, inserted between said valve andsaid needle; a sealed container (50) containing the transporter liquid(52) and connected to the valve (48) by a tube, a pump (54) of theintake and delivery type, in communication with the container (50) andserving to place the latter at a raised pressure or at a reducedpressure so as to cause the transporter liquid (52) to flow through thesaid duct (42, 44) in one direction or the other, and electronic means(58, 60) responding to the said measurement means (46) and acting bothon the said valve (48) and on the said pump (54) so as to cause adetermined amount of fluid (30) to be drawn up into the needle (12) tobe dispensed, means (60) of calculating the amount of fluid drawn intoor delivered through the needle, on the basis of the informationsupplied by the flow measurement means, and a control circuit (58)placed under the command of the said calculating means (60) and mainlyperforming the functions of controlling the pump (54) to place the saidcontainer (50) at a raised pressure or at a reduced pressure and ofcommanding the opening and closing of the valve (48) so as to allow ordisallow the displacement of a determined amount of transport liquid(52) in one direction or the other, said displacement causing adetermined amount of fluid (30) to be drawn into said needle (12) to bedispensed.
 2. Fluid dispensing device according to claim 1,characterized in that the said duct (42, 44) is formed inside anelongate body (36) bearing, at its respective ends (38), the said valve(48) and the said needle (12) and, in its central portion (40), the saidflow measurement means (46) which are inserted in the path of the duct(42, 44), in communication therewith.
 3. Fluid dispensing deviceaccording to claim 1, characterized in that the said duct (42, 44) isformed inside an elongate body (36) bearing, at its respective ends(38), the said valve (48) and the said needle (12), and in that the saidflow measurement means are inserted in the path of the duct (42)upstream of the said valve (48), in communication with this duct. 4.Fluid dispensing device according to claim 1, characterized in that thesaid flow measurement means (46) are of the type that provides ameasurement of the pressure difference between two points on the ductand a measurement of the temperature.
 5. Fluid dispensing deviceaccording to claim 4, characterized in that the said electronic means(58, 60) are designed to analyse information from the flow measurementmeans (46) and to provide information on the conditions of dispensing ofthe said fluid.
 6. Fluid dispensing device according to claim 1characterized in that the said calculating means (60) hold, in memory,the values of the viscosity of the transport liquid (52) as a functionof temperature and are programmed to calculate, on the basis of thepressure and temperature information delivered by the said flowmeasurement means (46), the amount of fluid drawn into or deliveredthrough the needle (12).